Yan Yi, Zhao Aonan, Qui Yinghui, Li Yuanyuan, Yan Ran, Wang Ying, Xu Wei, Deng Yulei
Department of Neurology, Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Neurology, Ruijin Hospital, Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Aging Neurosci. 2020 Feb 4;12:16. doi: 10.3389/fnagi.2020.00016. eCollection 2020.
This study aimed to explore the relationship between 18 single nucleotide polymorphisms (SNPs) and Alzheimer's disease (AD) within the southern Chinese population.
A total of 420 participants, consisting of 215 AD patients and 205 sex- and age-matched controls, were recruited. The SNaPshot technique and polymer chain reaction (PCR) were used to detect the 18 SNPs. Combined with the () ε4 allele and age at onset, we performed an association analysis between these SNPs and AD susceptibility. Furthermore, we analyzed SNP-associated gene expression using the expression quantitative trait loci analysis.
Our study found that rs17125924 of was associated with the risk of developing AD in the dominant ( = 0.022, odds ratio [OR] = 1.57, 95% confidence interval [CI]: 1.07-2.32) and overdominant ( = 0.005, OR = 1.76, 95% CI: 1.18-2.61) models. Moreover, compared with ε4 non-carriers, the frequency of the G-allele at rs17125924 was significantly higher among AD patients in ε4 allele carriers ( = 0.029). The rs9271058 of (dominant, overdominant, and additive models), rs9473117 of (dominant and additive models), and rs73223431 of (dominant, overdominant, and additive models) were associated with early onset AD (EOAD). Using the genotype-tissue expression (GTEx) and Braineac database, we found a significant association between rs9271058 genotypes and expression levels, while the CC genotype at rs9473117 and the TT genotype of rs73223431 increased and gene expression, respectively.
Our study identifies the G-allele at rs17125924 as a risk factor for developing AD, especially in ε4 carriers. In addition, we found that rs9271058 of , rs9473117 of , and rs73223431 of were associated with EOAD. Further studies with larger sample sizes are needed to confirm our results.
本研究旨在探讨中国南方人群中18个单核苷酸多态性（SNP）与阿尔茨海默病（AD）之间的关系。
共招募了420名参与者，包括215例AD患者和205名年龄及性别匹配的对照。采用SNaPshot技术和聚合酶链反应（PCR）检测这18个SNP。结合（）ε4等位基因和发病年龄，我们对这些SNP与AD易感性进行了关联分析。此外，我们使用表达数量性状位点分析来分析SNP相关的基因表达。
我们的研究发现，（基因）的rs17125924在显性模型（P = 0.022，优势比[OR] = 1.57，95%置信区间[CI]：1.07 - 2.32）和超显性模型（P = 0.005，OR = 1.76，95% CI：1.18 - 2.61）中与患AD的风险相关。此外，与ε4非携带者相比，rs17125924处G等位基因在ε4等位基因携带者的AD患者中的频率显著更高（P = 0.029）。（基因）的rs9271058（显性、超显性和加性模型）、（基因）的rs9473117（显性和加性模型）以及（基因）的rs73223431（显性、超显性和加性模型）与早发型AD（EOAD）相关。使用基因型 - 组织表达（GTEx）和Braineac数据库，我们发现rs9271058基因型与（基因）表达水平之间存在显著关联，而rs9473117处的CC基因型和rs73223431的TT基因型分别增加了（相关基因）和（相关基因）的表达。
我们的研究确定rs17125924处的G等位基因为患AD的一个风险因素，尤其是在ε4携带者中。此外，我们发现（基因）的rs9271058、（基因）的rs9473117和（基因）的rs73223431与EOAD相关。需要更大样本量的进一步研究来证实我们的结果。
